Alpha1-adrenergic receptor (α1AR) stimulation mediates sympathetic nervous system responses such as vascular smooth muscle contraction and myocardial hypertrophy. α1AR-mediated vasoconstriction contributes to baseline (tonic) vessel tone, modulates systemic vascular resistance/venous capacitance, and is important in cardiovascular responses to shock.1 in addition, during “fight and flight” responses, elevated catecholamines result in constriction of “nonessential” vascular beds (e.g. splanchnic) while blood flow to vital organs (e.g., brain, heart) remains uncompromised.2,3 cDNAs encoding three human α1AR subtypes (α1a, α1b and α1d4,5) were recently cloned, each expressed receptor pharmacologically characterized,4 and species heterogeneity in α1AR subtype tissue distribution identified.6,7 All three α1ARs couple predominantly via Gq to phospholipase C-b activation, resulting in formation of inositol trisphosphate (IP3), calcium release from intracellular stores, and ultimately to smooth muscle contraction.8 
Although reasons for existence of three α1AR subtypes remain elusive, recent findings suggest subtype and tissue specific regulation may be important.9,10 While all α1AR subtypes mediate smooth muscle contraction, hypertrophic pathways demonstrate subtype specific signaling.11 α1AR agonist exposure to neonatal rat myocytes results in α1aAR mRNA/protein upregulation (doubling) concurrent with α1b and α1d downregulation, correlating with induction of myocardial hypertrophy.12 In contrast, insulin and insulin-like growth factor I induces α1dAR expression in cultured rat vascular smooth muscle cells.13 Hence agonist exposure, disease states, and drugs alter α1AR subtype expression.
The present invention results, at least in part, from studies designed to determine the mechanisms underlying cardiovascular responses to acute stress and chronic catecholamine exposure (e.g. aging). Human vascular a1AR subtype distribution and function were examined. Specifically, two hypotheses were tested: 1) human α1AR subtype expression differs with vascular bed, and 2) age influences human vascular α1AR subtype expression. The results demonstrate human vascular α1AR subtype distribution differs from animal models, varies with vessel bed, correlates with contraction in mammary artery, and is modulated by aging.